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Protoplasmic astrocyte proximal to a blood vessel. Metallic impregnation Ramon Y Cajal. Ob. 20x. Human brain (personal collection).
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The goal of this review is to integrate - in its two parts - the considerable amount of information that has accumulated during these recent years over the morphology, biology and functions of astrocytes - first part - and to illustrate the active role of these cells in pathophysiological processes implicated in various psychiatric and neurologic d...
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... AS are found in all regions of the brain, including the cerebrum, cerebellum, and brainstem. They are also found in the grey matter and white matter of the spinal cord, but are also present in retina, epiphysis, and neurohypophysis [2][3][4]. There are numerous subtypes of AS [2,3,5,6]. ...
... The protoplasmic AS which reside in the grey matter of the CNS have fewer glial filaments [7] and ovoid or irregular cellular bodies with numerous, short, dichotomized processes [9,10]. Bergmann glial cells or epithelial glial cells are AS with long processes located in the granular layers of the cerebellar cortex [4]. Interlaminar AS are specific for humans and primates, the same as AS with varicose projection [8,[11][12][13]. ...
Astrocytes (AS) are the most abundant glial cells in the central nervous system (CNS). They have various morphologies and numerous (50-60) branching prolongations, with roles in the maintenance of the CNS function and homeostasis. AS in the optic nerve head (ONH) have specific distribution and function and are involved in the pathogenesis of glaucoma and other neural diseases, modify their morphologies, location, immune phenotype, and ultrastructure, thus being the key players in the active remodeling processes of the ONH.
... Astrocytes, representing roughly 20-40% of all glial cells in the cerebral gray matter [20,21], first originate during embryonic development from progenitor cells or radial glia which then mature throughout early postnatal development into astrocytes [22]. Defined morphologically by their star-like appearance given their numerous and complex processes [23], astrocytes are characterized, at the ultrastructural level, by their angular and thin processes often interacting with synaptic elements, their intermediate filaments, and the accumulation of glycogen granules [24]. Astrocytes can help protect brain homeostasis through the clearance of parenchymal metabolic waste through the glymphatic system [25][26][27][28], the regulation of cerebral blood flow, the maintenance of the blood-brain barrier [29][30][31][32], and are highly involved in synaptic activity and plasticity (synaptogenesis, maintenance, maturation, and elimination) [33][34][35][36][37]. Known for their key role in neuronal metabolic support, astrocytes can help maintain brain functions in numerous ways; for instance, by transforming the exocytotoxic glutamate released by post-synaptic dendritic spines into glutamine, which can be recycled back by synaptic elements [38,39]. ...
The past decade has witnessed increasing evidence for a crucial role played by glial cells, notably astrocytes, in Alzheimer’s disease (AD). To provide novel insights into the roles of astrocytes in the pathophysiology of AD, we performed a quantitative ultrastructural characterization of their intracellular contents and parenchymal interactions in an aged mouse model of AD pathology, as aging is considered the main risk factor for developing AD. We compared 20-month-old APP-PS1 and age-matched C57BL/6J male mice, among the ventral hippocampus CA1 strata lacunosum-moleculare and radiatum, two hippocampal layers severely affected by AD pathology. Astrocytes in both layers interacted more with synaptic elements and displayed more ultrastructural markers of increased phagolysosomal activity in APP-PS1 versus C57BL6/J mice. In addition, we investigated the ultrastructural heterogeneity of astrocytes, describing in the two examined layers a dark astrocytic state that we characterized in terms of distribution, interactions with AD hallmarks, and intracellular contents. This electron-dense astrocytic state, termed dark astrocytes, was observed throughout the hippocampal parenchyma, closely associated with the vasculature, and possessed several ultrastructural markers of cellular stress. A case study exploring the hippocampal head of an aged human post-mortem brain sample also revealed the presence of a similar electron-dense, dark astrocytic state. Overall, our study provides the first ultrastructural quantitative analysis of astrocytes among the hippocampus in aged AD pathology, as well as a thorough characterization of a dark astrocytic state conserved from mouse to human.
... The prefrontal cortex (PFC) is an area commonly implicated in major depression disorders (Schubert, et al., 2015;Fogaça and Duman, 2019). Synaptophysin is an integral membrane glycoprotein present in presynaptic vesicles of all neurons and is involved in synaptic transmission, synaptic biogenesis, initiating neurotransmitter release, synaptic vesicle endocytosis, and synapse formation (Gudi et al., 2017) while astrocytes are specialized glial cells which provide structural and functional support for neurons (Şovrea and Boşca, 2013). This study aimed to assess the mechanism of possible antidepressant effects of NAC by evaluating changes in PFC histology, synaptophysin, and astrocytes activities in addition to behavioral changes in the FST indexes and anhedonia status in the animal FST model. ...
Introduction:
The model for screening antidepressant-like activity in pre-clinical drug studies include, rat forced swimming test (FST). The reports on N-acetylcysteine (NAC) as an antioxidant supplement in stress related disorder is well documented. This study was aimed at potential antidepressant mechanism of N-Acetyl Cysteine (NAC), a glutamate precursor on FST animal model for screening antidepressant drugs using fluoxetine, a selective serotonin reuptake inhibitors (SSRIs) as standard antidepressant drug.
Methods:
Thirty adult male Wistar rats used for this study were randomly divided into six groups each with five (n=5) rats. The control group (A) received 1 ml of normal saline daily, group B served as the FST model, group C received 200mg/kg/day of NAC, group D received 20mg/kg/day of fluoxetine, group E the FST model treated with 200mg/kg/day of NAC, and F is the FST model treated with 20mg/kg/day of fluoxetine. Drugs were given orally. The effects of NAC on brain weights, the FST paradigms, sucrose preference test (SPT) for anhedonia were assessed and data analyzed using ANOVA where Tukey post-hoc test for statistical significance was set at (p < 0.05). The brains fixed in 4% paraformaldehyde, were processed and the paraffin embedded tissue were serially sectioned at 5 μm thick to be stained using Haematoxylin and Eosin (H and E) stain, immuno-histochemistry for synaptophysin (p38) and astrocytes (GFAP) activities in the prefrontal cortex (PFC).
Results:
Findings showed that NAC prevented FST-induced anxiety-like behaviors demonstrated by an increased SPT (that alleviates anhedonia), mobility time, and reduced immobility time. NAC caused an increase in brain weights and prevented FST-induced neurodegeneration, the proliferation of reactive astrocytes, and diminished synaptophysin immunoreactivity in the PFC similar to that seen in fluoxetine a standard anti-depressant drug.
Conclusion:
NAC treatment significantly exhibits its neuroprotective mechanism via inhibiting the proliferation of reactive astrocytes, which protects neurons and synapses from oxidative tissue damage induced by FST, hence an increase in synaptophysin activity that culminates in increased neural activity, increased SPT, and reduced immobility time.
... Macroglial cells, also called astrocytes, are specialized for the structural and functional support of neurons, being present in all regions of the central nervous system (CNS); inhere they perform two, essential, but different, functions: defense, by forming the blood-brain barrier (BBB), and maintenance of the homeostasis, by regulating cerebral blood flow, neuronal metabolism, and neurotransmitter' secretion [70]. ...
This article is a review of new advances in histology, concerning either classification or structure of different tissular elements (basement membrane, hemidesmosomes, urothelium, glandular epithelia, adipose tissue, astrocytes), and various organs' constituents (blood-brain barrier, human dental cementum, tubarial salivary glands, hepatic stellate cells, pineal gland, fibroblasts of renal interstitium, Leydig testicular cells, ovarian hilar cells), as well as novel biotechnological techniques (tissue engineering in angiogenesis), recently introduced.
... Astrocytes are specialized neuroglial cells found in the entire CNS and involved in many complex functions in healthy CNS, such as providing structural and functional support for neurons (Şovrea and Boşca, 2013), regulating the communication between already formed synaptic connections (Ota et al., 2013), participating in the control of brain homeostasis and the intrinsic brain defense system (Kettenmann and Verkhratsky, 2011). Astrocytes respond to all forms of CNS insults by a process called reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions (Sofroniew and Vinters, 2010). ...
Diethylnitrosamine (DEN), a known toxin and potent carcinogen induces oxidative stress by generation of free radicals resulting in cellular injury through its metabolized end product. There is dearth of information on DEN neurotoxicity. This study therefore, evaluated the oxidative damage and morphological changes induced by DEN in the cerebellum of Wistar rat. Twenty male Wistar rats weighing between 110 and 120 g were divided into two groups (n=10). Group I rats received distilled water and served as the control group, while group II rats received 25 mg/kg body weight of DEN i.p. twice weekly for 12 weeks. At the end of the administration, the rats from both groups were weighed and killed. The brains were weighed and the cerebella dissected out, some preserved in phosphate buffered saline for oxidative stress and antioxidant markers, while others fixed in 10% formol-saline for histological and immunohistochemical (Glial fibrillary acidic protein, GFAP) studies, for cerebellar cytoarchitecture and astrocytes population, respectively. Data were analyzed employing the unpaired student's t-test at p<0.05. There was a significant decrease in weight gain in the DEN-treated group, increased lipid peroxidation, decreased glutathione levels, superoxide dismutase activity and compared with the control rats at p<0.05. Histological and histomorphometric evaluation of the cerebellar cortex of DEN-treated rats showed pyknosis of the Purkinje cells with chromatolysis, significant reduction in the diameter/size and loss of the Purkinje cells compared with the control rats. Immunohistochemically, there was increased population of astrocytes in the DEN-treated rats compared with the control rats. The results of the study shows that prolonged exposure of rats to diethylnitrosamine induced oxidative stress with morphological alterations in the cerebellum and thus increasing the literature of diethylnitrosamine neurotoxicity.
... Astrocyte reaction to certain stimuli is defined by a wide range of heterogeneous responses, including changes in morphology [7,47]. To analyse the effect of oxysterols on astrocyte morphology and survival, cells were exposed to increasing concentrations of the Early and Late mixtures (1, 5 or 10 μM). ...
Among Alzheimer's disease (AD) brain hallmarks, the presence of reactive astrocytes was demonstrated to correlate with neuronal loss and cognitive deficits. Evidence indeed supports the role of reactive astrocytes as mediators of changes in neurons, including synapses. However, the complexity and the outcomes of astrocyte reactivity are far from being completely elucidated. Another key role in AD pathogenesis is played by alterations in brain cholesterol metabolism. Oxysterols (cholesterol oxidation products) are crucial for brain cholesterol homeostasis, and we previously demonstrated that changes in the brain levels of various oxysterols correlate with AD progression. Moreover, oxysterols have been shown to contribute to various pathological mechanisms involved in AD pathogenesis. In order to deepen the role of oxysterols in AD, we investigated whether they could contribute to astrocyte reactivity, and consequently impact on neuronal health.
Results
showed that oxysterols present in mild or severe AD brains induce a clear morphological change in mouse primary astrocytes, accompanied by the upregulation of some reactive astrocyte markers, including lipocalin-2 (Lcn2). Moreover, astrocyte conditioned media analysis revealed a significant increase in the release of Lcn2, cytokines, and chemokines in response to oxysterols. A significant reduction of postsynaptic density protein 95 (PSD95) and a concurrent increase in cleaved caspase-3 protein levels have been demonstrated in neurons co-cultured with oxysterol-treated astrocytes, pointing out that mediators released by astrocytes have an impact on neurons. Among these mediators, Lcn2 has been demonstrated to play a major role on synapses, affecting neurite morphology and decreasing dendritic spine density. These data demonstrated that oxysterols present in the AD brain promote astrocyte reactivity, determining the release of several mediators that affect neuronal health and synapses. Lcn2 has been shown to exert a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.
... Dysfunction of astrocytes has been indicated in numerous pathologies, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), Rett syndrome (RS), and Alexander's disease [6,7]. Recent studies showed that astrocytes can convert to reactive astrocytes under injury conditions [8][9][10][11][12][13][14][15][16][17]. These reactive astrocytes also express markers of mature "resting" astrocytes, including glial fibrillary acidic protein (GFAP), S100β, aquaporin-4, Cx30, Aldh1L1 proteins, and stem cell markers such as NESTIN [18]. ...
Astrocytes play the key roles in the physiology and pathology of the CNS. Thereupon, in this manuscript, we aim to demonstrate that the protocol for purification and culture of astrocytes is useful not only in 2 days postnatal but also in adult rat brain. Also, the mentioned protocol is a simple and efficient primary cell culture technique. The whole-brain was isolated from the skull and the meninges were removed carefully. Afterward, the cerebral hemispheres were mechanically and enzymatically digested. Then, the cell suspension was seeded in T25 culture flask and was incubated at 37 °C in the CO2 incubator. The first shaking was performed after 7–8 days and on day 14, second shaking was done. After 2–3 passage, the culture was analyzed. By passaging, the majority of extracted cells were astrocytes presenting with a polygonal to fusiform and flat morphology that expressed GFAP, GLAST, and S100β. The expression of neural, neuronal and oligodendrocyte markers was not detected in extracted cells. The patch-clamp recording comfirmed the purity of isolated astrocytes as well. The isolated cells from adult rat brain were astrocytes that expressed specific astrocyte markers after 3 and 10 passages. This method is suggested to obtain a population of astrocytes that may provide a beneficial tool for different neurophysiological and pathophysiological studies.
Graphic abstract
... Astrocytes are specialised glial cells which provide structural and functional support for neurons (Şovrea and Boşca, 2013). They are involved in synaptogenesis, and in regulating the communication between already formed synaptic connections (Ota, Zanetti and Hallock., 2013). ...
Introduction:
This study aimed at assessing the protective mechanisms of Kolaviron (KV) on the cerebellum in a rat model of demyelination.
Methods:
Twenty-eight male Wistar rats were used in the present study. They were randomly divided into 4 groups of 7 rats. Group A (control) received corn oil (0.5 mL/kg/d); group B received 0.2% Cuprizone (CPZ); group C was treated with 200 mg/kg/d of KV, and group D received 0.2% CPZ and 200 mg/kg/d KV for 6 weeks. CPZ powder was mixed with the regular diet while KV was dissolved in corn oil and administered orally. A behavioral test was conducted at the termination of the experiment. Thereafter, the animals were sacrificed and their brains were removed with the excision of the cerebellum. A part of the cerebelli underwent tissue processing with a series of 5 μm thick sections cut from paraffin blocks for histological and immunohistochemical assessment. Besides, the remaining cerebellar tissues were homogenized for the spectrophotometric assays of Oxidative Stress (OS) parameters.
Results:
The current research findings revealed minimal weight gain following CPZ treatment, but significant weight increase in KV-treated rats. CPZ treatment was associated with a reduction in the number of the line crossed, rearing frequency, rearing duration, center square entry, and center square duration; however, it increased the freezing time, i.e. significantly reversed in the KV-treated animals. Oxidative markers, such as Superoxide Dismutase (SOD) and GPx were reduced in CPZ-treated rats with elevated MDA levels. However, these data were significantly reversed by the co-administration of CPZ and KV. At the tissue level, the cerebellar cortex was characterized by poorly defined layers, cryptic granules, as well as chromatolysis and pyknotic Purkinje cells with the evidence of hypertrophic astrogliosis.
Conclusion:
CPZ treatment significantly depressed locomotor and exploratory activities. Furthermore, it increased OS and cerebellar toxicity. However, KV intervention significantly enhanced behavioral functions and ameliorated CPZ-induced cerebellar degeneration. Moreover, it considerably regulated OS markers in the cerebellum of the rat model of demyelinating diseases.
... It has been reported that in AD patients, disruption of the processes of these interlaminar astrocytes is correlated with dysfunction in neuronal transmission support 34 . In the present study, the longer or thicker astrocytic processes found in layer I/II extended to layer III to IV, where the astrocytic processes may play important roles in the synaptic transmission of neurons connected to the CA1 region 35,36 . ...
Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.
... The difference of the glial precursors, as well as the site of which the varied differentiation pathways initiates, can explain this heterogeneity [82]. During fetal development, astrocytes are immature and have high proliferative activity. ...
... In humans, the maturity stage is reached about 6 to 12 months after birth, when differentiation reaches the final stage [81,83]. Cells from the radial glia of the embryonic ventricular zone as well as intermediate progenitors from neonatal subventricular zones give rise to protoplasmic astrocytes, whereas fibrous astrocytes originate mostly from neonatal progenitors of the subventricular zone [79,82]. Focusing on the spinal cord, the development and distribution of astrocytes in this site are associated with transcription factors expressed by glial progenitor cell [84], and can share components involved in neurogenesis of oligodendrocytes, such as the Ascl1 transcription factor. ...
... However these cells are outside the CNS, for instance, keratinocytes and liver cells are also able to express GFAP [79]. The enzyme aldehyde dehydrogenase (AldhL1) and the glutamate transporter GLT-1 are expressed by all astrocytes [82,86]. These enzymes have also been used as a cellular marker, whereas the calcium-binding protein S100B and the Kir4.1 channel, for example, are considered as astrocyte subtype-specific markers [82,86]. ...
